Enzo Vicari

Diabetes mellitus and sperm parameters.

Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged by findings showing that DM induces subtle molecular changes that are important for sperm quality and function. This brief review shows the main sperm parameters in patients with DM and presents the mechanisms hypothesized to explain the changes observed in these patients. The data available suggest that DM alters conventional sperm parameters. In addition, DM causes histologic damage of the epididymis, with a negative impact on sperm transit. Various mechanisms may explain the sperm damage observed in patients with DM. These include endocrine disorders, neuropathy, and increased oxidative stress. Many authors suggest that DM decreases serum testosterone levels. This is associated with a steroidogenetic defect in Leydig cells. In addition, diabetic neuropathy seems to cause atonia of seminal vesicles, bladder, and urethra. Furthermore, DM is associated with an increased oxidative stress, which damages sperm nuclear and mitochondrial DNA. Finally, spermatogenesis derangement and germ cell apoptosis in type 1 DM may relate to a local autoimmune damage, whereas insulin resistance, obesity, and other related comorbidities may impair sperm parameters and decrease testosterone serum levels in patients with type 2 DM.

Antioxidant treatment with carnitines is effective in infertile patients with prostatovesiculoepididymitis and elevated seminal leukocyte concentrations after treatment with nonsteroidal anti-inflammatory compounds

OBJECTIVE To evaluate whether the association of antioxidants and anti-inflammatory compounds may be beneficial in treatment of patients with abacterial prostatovesiculoepididymitis (PVE) and elevated seminal leukocyte concentrations. DESIGN Open, prospective, random study. SETTING Academic research environment. PATIENT(S) Ninety-eight patients with PVE who had increased seminal leukocyte concentrations (>1 x 10(6) cells/mL). Carnitines (group A; n = 30) or nonsteroidal anti-inflammatory drugs (group B; n = 16) for 4 months; nonsteroidal anti-inflammatory drugs for 2 months, followed by treatment with carnitines for 2 months (group C; n = 26); or nonsteroidal anti-inflammatory treatment given concomitantly with carnitines (group D; n = 26) for 4 months. MAIN OUTCOME MEASURE(S) Semen variables, production of reactive oxygen species, and pregnancy outcome were evaluated before and after treatment and following a 3-month washout period. RESULT(S) Patients in group C had the highest reduction in production of reactive oxygen species associated with increased sperm motility and viability. Groups B and D experienced intermediate effects, and group A experienced the least effect. CONCLUSION(S) Antioxidant treatment with carnitines is effective in patients with abacterial PVE and increased seminal leukocyte concentrations if these patients have been pretreated with nonsteroidal anti-inflammatory drugs.

Sperm aneuploidy in infertile men

A recent line of research has shown that infertile male patients produce cytogenetically abnormal spermatozoa, despite a normal somatic karyotype, as a result of an altered intra-testicular environment that affects negatively the mechanisms controlling chromosome segregation during cell division. The rate of aneuploid spermatozoa production is significantly higher in patients with abnormal sperm parameters compared with those of normozoospermic subjects or infertile patients with normal sperm parameters. All chromosomes are subject to aneuploidy, although at a different rate; the heterochromosomes are more often altered than are the autosomes. A negative correlation has been reported to exist between aneuploidy and the main sperm parameters, suggesting that greater testicular damage is associated with a greater chance of chromosome malsegregation events. Abnormally-shaped spermatozoa are more likely to have chromosome abnormalities, particularly those with an enlarged head. More studies are necessary, however, to evaluate whether other types of sperm head abnormalities are also associated with an abnormal sperm chromosome complement. The possibility of retrieving testicular or epididymal spermatozoa in patients with azoospermia and using them in assisted reproduction techniques has prompted the evaluation of their chromosomal status. Studies have shown that testicular and epididymal spermatozoa have a greater rate of aneuploidy compared with that of ejaculated spermatozoa. Some authors have also shown that patients with non-obstructive azoospermia have a significantly higher sperm aneuploidy rate compared with that of patients with obstructive azoospermia. Sperm aneuploidy seems to have a negative impact on assisted reproduction technique outcome. Although it does not affect the fertilization rate, an elevated sperm aneuploidy rate is associated with a greater rate of pregnancy failure. Nevertheless, some patients with elevated sperm aneuploidy rate can still achieve a pregnancy, but with an increased risk of generating an aneuploid offspring. Thus, sperm aneuploidy evaluation is recommended in infertile patients with abnormal semen parameters, particularly if they undergo IVF programmes.

Does alcohol have any effect on male reproductive function? A review of literature

Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.

Effects of varicocelectomy on sperm DNA fragmentation, mitochondrial function, chromatin condensation, and apoptosis.

The aim of this study was to evaluate conventional semen parameters (density, morphology, and progressive motility) and the flow-cytometric parameters of DNA fragmentation, mitochondrial membrane potential, phosphatidylserine externalization, and chromatin compactness in patients with varicocele before and after varicocelectomy. Thirty men (26.5 ± 3.2 years old, range 20-32 years) with oligoasthenoteratozoospermia and grade 3 left varicocele were selected (without other causes of male infertility). Each of them underwent sperm analysis and flow cytometric evaluation before and 4 months after subinguinal microsurgical varicocelectomy (SMV). After varicocelectomy, men had significantly higher sperm density, progressive motility, and normal forms compared with baseline. They also had a significantly lower percentage of spermatozoa with low mitochondrial membrane potential. After SMV, they showed a significantly lower percentage of spermatozoa with phosphatidylserine externalization, an early sign of apoptosis. Significantly decreased percentages of spermatozoa with abnormal chromatin compactness and spermatozoa with DNA fragmentation were found after SMV compared with baseline. Subinguinal microsurgical varicocelectomy improves sperm function in oligoasthenoteratozoospermia secondary to grade 3 left varicocele. Improvements are seen in conventional parameters and biofunctional parameters not routinely evaluated.

Negative effect of increased body weight on sperm conventional and nonconventional flow cytometric sperm parameters.

Although with some discrepancy, obese men have been reported to have the worst conventional sperm parameters, but little is known about the effects of body weight on sperm mitochondrial function, chromatin condensation and apoptosis. This study was undertaken to evaluate conventional and nonconventional sperm parameters in nonsmoking overweight or obese men without any other cause known to alter sperm parameters. Fifty overweight, 50 obese, and 50 normal-weight healthy nonsmoking men were carefully selected. Each man underwent up to 2 sperm analyses and evaluation of mitochondrial membrane potential (MMP), phosphatidylserine (PS) externalization, chromatin compactness, and DNA fragmentation by flow cytometry. Overweight and obese men had significantly lower sperm progressive motility and normal forms than controls. They also had a significantly higher percentage of spermatozoa with low MMP. Obese, but not overweight, men showed a significantly higher percentage of spermatozoa with PS externalization, an early sign of apoptosis, and a lower percentage of viable spermatozoa. A significant increased percentage of spermatozoa with abnormal chromatin compactness was found in both overweight and obese men, whereas only obese men had a significantly higher number of spermatozoa with DNA fragmentation compared with controls. Healthy nonsmoking overweight and obese men have worse conventional and nonconventional sperm parameters than normal-weight controls. The important role played by these parameters in a couples fertility suggests a program of body weight loss among the therapeutic repertoire for male infertility.

Myoinositol: Does It Improve Sperm Mitochondrial Function and Sperm Motility?

OBJECTIVE To evaluate whether an improvement in mitochondrial membrane potential was associated with sperm motility amelioration and greater sperm recovery after the swim-up procedure. A second purpose was to evaluate the effects of myoinositol (MYO) on sperm apoptosis, quality of chromatin compaction, and DNA integrity. METHODS Spermatozoa from 20 normozoospermic men and 20 patients with oligo-astheno-teratozoospermia were incubated in vitro with 2 mg/mL of MYO or phosphate-buffered saline as a control for 2 hours. After this incubation period, sperm motility was evaluated. Flow cytometry was used to analyze the mitochondrial membrane potential, phosphatidylserine externalization, chromatin compactness, and DNA fragmentation. We also evaluated the total number of motile spermatozoa recovered after swim-up after incubation with MYO or phosphate-buffered saline. RESULTS MYO significantly increased the percentage of spermatozoa with progressive motility in both normozoospermic men and patients with oligo-astheno-teratozoospermia. Motility improvement in the latter group was associated with a significant increase in the percentage of spermatozoa with high mitochondrial membrane potential. MYO had no effects on mitochondrial function in spermatozoa from normozoospermic men. Sperm phosphatidylserine externalization, chromatin compactness, and DNA fragmentation were unaffected by MYO in both groups. After incubation with MYO, the total number of spermatozoa recovered after swim-up had improved significantly in both groups. CONCLUSION These data show that MYO increases sperm motility and the number of spermatozoa retrieved after swim-up in both normozoospermic men and patients with abnormal sperm parameters. In patients with oligo-astheno-teratozoospermia, the improvement in these parameters was associated with improved sperm mitochondrial function. These findings support the use of MYO in both in vivo- and in vitro-assisted reproductive techniques.

Circulating Endothelial Progenitor Cells and Endothelial Microparticles in Patients With Arterial Erectile Dysfunction and Metabolic Syndrome

Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial erectile dysfunction (ED) and metabolic syndrome (MetS). To accomplish this, 100 patients (ages 45-60 years) with ED and MetS (Adult Treatment Panel III [ATP III] 1999 criteria) and 17 healthy men (ages 44-57 years) were selected. EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD144(pos)/Annexin V(pos)) blood concentrations were evaluated by flow cytometry, before and after administration of tadalafil (20 mg) on demand for 3 months. Before treatment, EPCs and EMPs were significantly higher in patients compared with healthy men. EPCs increased significantly after tadalafil administration, whereas EMPs did not differ significantly. EPCs correlated positively or negatively with body mass index and with some cavernous artery indices, both before and after tadalafil administration. EMPs showed only positive correlations with body mass index and some cavernous artery indices, both before and after tadalafil administration. Patients with arterial ED and MetS have higher EPCs and EMPs compared with healthy men; hence, these cells may be regarded as markers of cavernous artery dysfunction. Tadalafil administration increased EPCs but not EMPs, suggesting that this compound may play a role in the endothelial repair response.

Spontaneous transmission from a father to his son of a Y chromosome microdeletion involving the deleted in azoospermia (DAZ) gene

Microdeletions of the so-called azoospermia factor (AZF) locus of the Y chromosome long arm (Yq) have been recognized as an etiological factor of severe oligozoospermia or azoospermia. Because of this, patients affected are generally infertile unless assisted reproductive techniques are used. We report the case of an oligozoospermic patient (proband) who inherited an extensive Yq microdeletion from his father through a spontaneous pregnancy. Leukocyte DNA was extracted using a commercially available kit. A total of 22 pairs of sequence-tagged site (STSs) based primers, spanning the entire AZF region, were used for the screening. Both the proband and his father carried a Yq microdeletion of the most distal AZF subregion (AZFc) where the deleted in azoospermia (DAZ) gene is located. The proband’s father was a sixty-nine-yr-old man who had 3 other children, 2 females and 1 male. This case adds further evidence that the deletion of the DAZ gene is associated with different phenotypic expressions, including normal fertility.

Genetics of polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a reproductive system disorder characterized by irregular menses, anovulation, clinical and/or biochemical signs of hyperandrogenism (hirsutism and/or acne), ovarian micropolycystic appearance and metabolic abnormalities, such as hyperinsulinaemia and obesity. The aetiopathogenesis of this syndrome is not well known. Several pathogenetic hypotheses have been proposed to explain the full array of symptoms and signs, but with elusive results. A genetic abnormality causing PCOS is supported by the observation that different members of the same family are often affected, and about half of the sisters of PCOS women have elevated serum testosterone concentrations. Therefore, the presence of gene abnormalities in women with PCOS has been widely explored in the attempt to establish whether their mutations or polymorphisms may cause PCOS. The main genes evaluated are those involved in steroidogenesis, steroid hormone effects, gonadotrophin release regulation and action, insulin secretion and action, and adipose tissue metabolism. Despite the vast body of literature produced, none of the genes evaluated seems to play a key role in PCOS pathogenesis. It is likely that PCOS may represent the final outcome of different, deeply inter-related genetic abnormalities that influence each other and perpetuate the syndrome.